This proposed center will bring together a number of investigators with specialties in pharmacokinetics, clinical pharmacology, analytical methodology, drug metabolism, medicine, laboratory medicine, pediatrics, and biostatistics. The overall area of concern of the group is to investigate and model the relationship between drug kinetics and dynamics and to discover, understand and quantify the modifications to drug kinetics and/or dynamics caused by altered physiology (disease states). Fifteen projects divided into seven scientific units will examine and attempt to correlate input processes of drug into the body, distribution of drug into the general circulation and to sites of action and loss processes. These pharmacokinetic parameters will be correlated with pharmacodynamic measures of pharmacologic effect, clinical effect and toxicity.